tetano
Editor, Senior Moderator
Immunity
. 2024 Apr 26:S1074-7613(24)00214-0.
doi: 10.1016/j.immuni.2024.04.009. Online ahead of print. Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint
Matthew P Mulè[SUP] 1 [/SUP], Andrew J Martins[SUP] 2 [/SUP], Foo Cheung[SUP] 3 [/SUP], Rohit Farmer[SUP] 3 [/SUP], Brian A Sellers[SUP] 3 [/SUP], Juan A Quiel[SUP] 3 [/SUP], Arjun Jain[SUP] 2 [/SUP], Yuri Kotliarov[SUP] 3 [/SUP], Neha Bansal[SUP] 2 [/SUP], Jinguo Chen[SUP] 3 [/SUP], Pamela L Schwartzberg[SUP] 4 [/SUP], John S Tsang[SUP] 5 [/SUP]
Affiliations
Multimodal single-cell profiling methods can capture immune cell variations unfolding over time at the molecular, cellular, and population levels. Transforming these data into biological insights remains challenging. Here, we introduce a framework to integrate variations at the human population and single-cell levels in vaccination responses. Comparing responses following AS03-adjuvanted versus unadjuvanted influenza vaccines with CITE-seq revealed AS03-specific early (day 1) response phenotypes, including a B cell signature of elevated germinal center competition. A correlated network of cell-type-specific transcriptional states defined the baseline immune status associated with high antibody responders to the unadjuvanted vaccine. Certain innate subsets in the network appeared "naturally adjuvanted," with transcriptional states resembling those induced uniquely by AS03-adjuvanted vaccination. Consistently, CD14[SUP]+[/SUP] monocytes from high responders at baseline had elevated phospho-signaling responses to lipopolysaccharide stimulation. Our findings link baseline immune setpoints to early vaccine responses, with positive implications for adjuvant development and immune response engineering.
Keywords: adjuvants; computational biology; human immunology; immune homeostasis; immune regulation; influenza vaccination; innate immune response; multimodal immune monitoring; pandemic influenza vaccination; predictors of vaccine responses; single-cell analysis; systems immunology; vaccine response.
. 2024 Apr 26:S1074-7613(24)00214-0.
doi: 10.1016/j.immuni.2024.04.009. Online ahead of print. Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint
Matthew P Mulè[SUP] 1 [/SUP], Andrew J Martins[SUP] 2 [/SUP], Foo Cheung[SUP] 3 [/SUP], Rohit Farmer[SUP] 3 [/SUP], Brian A Sellers[SUP] 3 [/SUP], Juan A Quiel[SUP] 3 [/SUP], Arjun Jain[SUP] 2 [/SUP], Yuri Kotliarov[SUP] 3 [/SUP], Neha Bansal[SUP] 2 [/SUP], Jinguo Chen[SUP] 3 [/SUP], Pamela L Schwartzberg[SUP] 4 [/SUP], John S Tsang[SUP] 5 [/SUP]
Affiliations
- PMID: 38697118
- DOI: 10.1016/j.immuni.2024.04.009
Multimodal single-cell profiling methods can capture immune cell variations unfolding over time at the molecular, cellular, and population levels. Transforming these data into biological insights remains challenging. Here, we introduce a framework to integrate variations at the human population and single-cell levels in vaccination responses. Comparing responses following AS03-adjuvanted versus unadjuvanted influenza vaccines with CITE-seq revealed AS03-specific early (day 1) response phenotypes, including a B cell signature of elevated germinal center competition. A correlated network of cell-type-specific transcriptional states defined the baseline immune status associated with high antibody responders to the unadjuvanted vaccine. Certain innate subsets in the network appeared "naturally adjuvanted," with transcriptional states resembling those induced uniquely by AS03-adjuvanted vaccination. Consistently, CD14[SUP]+[/SUP] monocytes from high responders at baseline had elevated phospho-signaling responses to lipopolysaccharide stimulation. Our findings link baseline immune setpoints to early vaccine responses, with positive implications for adjuvant development and immune response engineering.
Keywords: adjuvants; computational biology; human immunology; immune homeostasis; immune regulation; influenza vaccination; innate immune response; multimodal immune monitoring; pandemic influenza vaccination; predictors of vaccine responses; single-cell analysis; systems immunology; vaccine response.